251 research outputs found

    Fixed Point Theorems for Random Variables in Complete Metric Spaces

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    In this paper  we prove some fixed point theorem for random variables with one and two self maps satisfying rational inequality in complete metric spaces Keywords: Random fixed point,Complete metric space, Common fixed points. Mathematics Subject Classification: 47H1

    The current state of animal models and genomic approaches towards identifying and validating molecular determinants of Mycobacterium tuberculosis infection and tuberculosis disease

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    Animal models are important in understanding both the pathogenesis of and immunity to tuberculosis (TB). Unfortunately, we are beginning to understand that no animal model perfectly recapitulates the human TB syndrome, which encompasses numerous different stages. Furthermore, Mycobacterium tuberculosis infection is a very heterogeneous event at both the levels of pathogenesis and immunity. This review seeks to establish the current understanding of TB pathogenesis and immunity, as validated in the animal models of TB in active use today. We especially focus on the use of modern genomic approaches in these models to determine the mechanism and the role of specific molecular pathways. Animal models have significantly enhanced our understanding of TB. Incorporation of contemporary technologies such as single cell transcriptomics, high-parameter flow cytometric immune profiling, proteomics, proteomic flow cytometry and immunocytometry into the animal models in use will further enhance our understanding of TB and facilitate the development of treatment and vaccination strategies

    Tribological investigation of HVOF-spray Cr3C2-25NiCr and WC-10Co-4Cr coated turbine steel under varied slurry erosion conditions

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    150-167In this work, high velocity oxy fuel (HVOF) method based spray coatings namely Cr3C2-25NiCr and WC-10Co-4Cr have been deposited on AISI304 turbine steels. An attempt has been made to analyze the coatings under accelerated slurry erosion conditions by employing a laboratory-developed slurry erosion testing set-up. The testing has been performed under varied conditions of slurry concentration, impact velocity and impact angle using the Taguchi approach. The microstructure of coating powder, erodent particles and deposited coatings have been studied using a scanning electron microscope (SEM) analysis. Erosion tests indicated that HVOF-spray Cr3C2-25NiCr and WC-10Co-4Cr coatings have been deposited on AISI304 steel exhibited significant improvements in the erosion resistance of AISI304 steel. The possible reason for such behaviour could be higher microhardness of HVOF-spray coatings in comparison with AISI304 bare steel. From SEM images of the samples taken prior and post slurry erosion tests, it has been observed that Cr3C2-25NiCr coating exhibited mixed (ductile and brittle) behaviour, though the WC-10Co-4Cr coating mostly demonstrated ductile behavior under conditions for erosion from the slurry. Apart from that, an attempt has been made to develop a functional equation based on the regression approach which could be employed to assess the erosion wear rate under a set of conditions. The predicted erosion wear results under varied conditions are in close relationship to experimental values

    Tribological investigation of HVOF-spray Cr3C2-25NiCr and WC-10Co-4Cr coated turbine steel under varied slurry erosion conditions

    Get PDF
    In this work, high velocity oxy fuel (HVOF) method based spray coatings namely Cr3C2-25NiCr and WC-10Co-4Cr have been deposited on AISI304 turbine steels. An attempt has been made to analyze the coatings under accelerated slurry erosion conditions by employing a laboratory-developed slurry erosion testing set-up. The testing has been performed under varied conditions of slurry concentration, impact velocity and impact angle using the Taguchi approach. The microstructure of coating powder, erodent particles and deposited coatings have been studied using a scanning electron microscope (SEM) analysis. Erosion tests indicated that HVOF-spray Cr3C2-25NiCr and WC-10Co-4Cr coatings have been deposited on AISI304 steel exhibited significant improvements in the erosion resistance of AISI304 steel. The possible reason for such behaviour could be higher microhardness of HVOF-spray coatings in comparison with AISI304 bare steel. From SEM images of the samples taken prior and post slurry erosion tests, it has been observed that Cr3C2-25NiCr coating exhibited mixed (ductile and brittle) behaviour, though the WC-10Co-4Cr coating mostly demonstrated ductile behavior under conditions for erosion from the slurry. Apart from that, an attempt has been made to develop a functional equation based on the regression approach which could be employed to assess the erosion wear rate under a set of conditions. The predicted erosion wear results under varied conditions are in close relationship to experimental values

    MicroRNA profiling reveals age-dependent differential expression of nuclear factor κB and mitogen-activated protein kinase in adipose and bone marrow-derived human mesenchymal stem cells

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    Introduction: Mesenchymal stem cells (MSCs) play a central role in mediating endogenous repair of cell and tissue damage. Biologic aging is a universal process that results in changes at the cellular and molecular levels. In the present study, the role of microRNA (miRNA) in age-induced molecular changes in MSCs derived from adipose tissue (ASCs) and bone marrow (BMSCs) from young and old human donors were investigated by using an unbiased genome-wide approach. Methods: Human ASCs and BMSCs from young and old donors were cultured, and total RNA was isolated. The miRNA fraction was enriched and used to determine the expression profile of miRNA in young and old donor MSCs. Based on miRNA expression, differences in donor MSCs were further investigated by using differentiation assays, Western blot, immunocytochemistry, and bioinformatics. Results: Biologic aging demonstrated reduced osteogenic and adipogenic potential in ASCs isolated from older donors, whereas cell size, complexity, and cell-surface markers remained intact with aging. Analysis of miRNA profiles revealed that small subsets of active miRNAs changed secondary to aging. Evaluation of miRNA showed significantly decreased levels of gene expression of inhibitory kappa B kinase (Iκ\kappaB), interleukin-1α\alpha, inducible nitric oxide synthase (iNOS), mitogen-activated protein kinase/p38, ERK1/2, c-fos, and c-jun in MSCs from older donors by both bioinformatics and Western blot analysis. Nuclear factor kappa B (NF-κ\kappaB), myc, and interleukin-4 receptor mRNA levels were significantly elevated in aged cells from both the adipose and bone marrow depots. Immunocytochemistry showed nuclear localization in young donors, but a cytosolic predominance of phosphorylated NF-κ\kappaB in ASCs from older donors. Western blot demonstrated significantly elevated levels of NF-κ\kappaB subunits, p65 and p50, and AKT. Conclusions: These findings suggest that differential expression of miRNA is an integral component of biologic aging in MSCs

    Myeloid-derived suppressor cells mediate T cell dysfunction in nonhuman primate TB granulomas

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    Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell population comprised of immature myeloid cells and myeloid progenitors with very potent immunosuppressive potential. MDSCs are reported to be abundant in the lungs of active tuberculosis (TB) patients. We sought to perform an in-depth study of MDSCs during latent TB infection (LTBI) and active TB (ATB) using the nonhuman primate (NHP) model of pulmonary TB. We found a higher proportion of granulocytic, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the lungs of ATB animals compared to those with LTBI or naive control animals. Active disease in the lung, but not LTBI, was furthermore associated with higher proliferation, expansion, and immunosuppressive capabilities of PMN-MDSCs, as shown by enhanced expression of Ki67, indoleamine 2,3-dioxygenase (IDO1), interleukin-10 (IL-10), matrix metallopeptidase 9 (MMP-9), inducible nitric oxide synthase (iNOS), and programmed death-ligand 1 (PD-L1). These immunosuppressive PMN-MDSCs specifically localized to the lymphocytic cuff at the periphery of the granulomas in animals with ATB. Conversely, these cells were scarcely distributed in interstitial lung tissue and the inner core of granulomas. This spatial regulation suggests an important immunomodulatory role of PMN-MDSCs by restricting T cell access to the TB granuloma core and can potentially explain dysfunctional anti-TB responses in active granuloma. Our results raise the possibility that the presence of MDSCs can serve as a biomarker for ATB, while their disappearance can indicate successful therapy. Furthermore, MDSCs may serve as a potential target cell for adjunctive TB therapy

    MicroRNA Profiling Reveals Age-Dependent Differential Expression of Nuclear Factor B and Mitogen-Activated Protein Kinase in Adipose and Bone Marrow-Derived Human Mesenchymal Stem Cells

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    Introduction. Mesenchymal stem cells (MSCs) play a central role in mediating endogenous repair of cell and tissue damage. Biologic aging is a universal process that results in changes at the cellular and molecular levels. In the present study, the role of microRNA (miRNA) in age-induced molecular changes in MSCs derived from adipose tissue (ASCs) and bone marrow (BMSCs) from young and old human donors were investigated by using an unbiased genome-wide approach. Methods. Human ASCs and BMSCs from young and old donors were cultured, and total RNA was isolated. The miRNA fraction was enriched and used to determine the expression profile of miRNA in young and old donor MSCs. Based on miRNA expression, differences in donor MSCs were further investigated by using differentiation assays, Western blot, immunocytochemistry, and bioinformatics. Results: Biologic aging demonstrated reduced osteogenic and adipogenic potential in ASCs isolated from older donors, whereas cell size, complexity, and cell-surface markers remained intact with aging. Analysis of miRNA profiles revealed that small subsets of active miRNAs changed secondary to aging. Evaluation of miRNA showed significantly decreased levels of gene expression of inhibitory kappa B kinase (IκB), interleukin-1α, inducible nitric oxide synthase (iNOS), mitogen-activated protein kinase/p38, ERK1/2, c-fos, and c-jun in MSCs from older donors by both bioinformatics and Western blot analysis. Nuclear factor kappa B (NF-κB), myc, and interleukin-4 receptor mRNA levels were significantly elevated in aged cells from both the adipose and bone marrow depots. Immunocytochemistry showed nuclear localization in young donors, but a cytosolic predominance of phosphorylated NF-κB in ASCs from older donors. Western blot demonstrated significantly elevated levels of NF-κB subunits, p65 and p50, and AKT. Conclusions: These findings suggest that differential expression of miRNA is an integral component of biologic aging in MSCs

    Development of Hot Melt Coating Technique for Taste Masking of Chloroquine Phosphate Tablets

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    In the present study to mask the unpleasant taste of chloroquine phosphate, hot melt coating technique was used as a taste masking tool. Hot melt coating is a solvent free technology grants rapid, additionally economical coating process with reduced risk of dissolving drug during process and provide uniform application rate of coating agent. Precirol ATO 5 was used as hot melt coating material for taste masking. Tablets were prepared by wet granulation method and coated using hot melt coating technique. Coated tablets exhibited good uniformity of drug content. Amount of drug release from all batches were evaluated. Taste evaluation of hot melt coated tablets was done by using electronic tongue.PrecirolATO5 was found to be a better taste masking agent when used by hot melt coating technique. Keywords: Precirol ATO 5, Hot melt coating, taste masking

    Visceral Leishmaniasis: An Overview and Integrated Analysis of the Current Status, Geographical Distribution and Its Transmission

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    Visceral leishmaniasis (VL) is a vector–borne disease transmitted by Phlebotomine sandflies, with up to 350 million people are at risk of developing infection globally. VL has a severe influence on the impoverished and undeveloped populations among several subcontinents. Early and accurate diagnosis and treatment remain crucial to the management of VL, which still depends on vector control. The present chapter objectives are to provide an overview of visceral leishmaniasis and to raise knowledge of the most recent progress in this condition’s management, treatment, and prevention. Additionally, this chapter could be helpful for comprehending the difficulties and knowledge gaps in eliminating this protozoan disease as well as for learning the planning lessons from the global management of diseases like malaria and tuberculosis

    Mycobacterium tuberculosis infection drives a type I IFN signature in lung lymphocytes

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    Mycobacterium tuberculosis (Mtb) infects 25% of the world\u27s population and causes tuberculosis (TB), which is a leading cause of death globally. A clear understanding of the dynamics of immune response at the cellular level is crucial to design better strategies to control TB. We use the single-cell RNA sequencing approach on lung lymphocytes derived from healthy and Mtb-infected mice. Our results show the enrichment of the type I IFN signature among the lymphoid cell clusters, as well as heat shock responses in natural killer (NK) cells from Mtb-infected mice lungs. We identify Ly6A as a lymphoid cell activation marker and validate its upregulation in activated lymphoid cells following infection. The cross-analysis of the type I IFN signature in human TB-infected peripheral blood samples further validates our results. These findings contribute toward understanding and characterizing the transcriptional parameters at a single-cell depth in a highly relevant and reproducible mouse model of TB
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